三株弓形虫对昆明鼠致病性的比较研究

Pathogenicity Comparison of Three Toxoplasma gondii Strains to Kunming Mice

刚地弓形虫是一种专性细胞内寄生原虫,弓形虫属仅有刚地弓形虫一种,但世界各地的分离株有着丰富的遗传多样性。作者以Ⅱ型(Pru、BJ)和Ⅲ型(VEG)虫株为研究对象,通过腹腔接种昆明小鼠,观察小鼠的临床表现,检测血清抗体水平、弓形虫在组织器官的动态分布及脑荷虫量等指标,比较不同虫株对小鼠致病性的差异。结果显示:Ⅱ型虫株接种小鼠表现出更明显的临床症状。监测小鼠血清抗体变化发现,Ⅱ型虫株感染小鼠在第4天即检测到弓形虫特异性抗体,随后抗体水平至第64天持续上升,感染Ⅲ型虫株小鼠血清在感染后第32天达到峰值并维持在较高水平。并且,三种虫株在小鼠组织器官的动态分布趋势大体相同,感染早期(第1天)侵染肺、肾、肌肉,中期(第8天)多分布在心、肺、肌肉、脑中,后期(第32天)存在于脑中,脾、肾、肝中不易检测到虫体。成功建立了三种弓形虫虫株感染昆明小鼠模型,证明Ⅱ型和Ⅲ型虫株对昆明鼠致病力的具体差异,并发现不同基因型弓形虫速殖子感染小鼠后在小鼠体内的分布随时间呈现一定的规律性,为弓形虫致病力的研究和动物模型的建立提供参考。

Toxoplasma gondii is an obligate protozoan parasite with only one species, but it has rich genetic diversity with very different virulence. We chose three strains of the only species： Pru, BJ, VEG strains to compare their pathogenicity after intraperitoneal injection in Kunming mouse. We evaluated their virulence by clinical symptoms, serum antibody level, organ distribution of parasites and brain burden. Our results showed that mice symptoms infected with type II was more significant than type III infected group. Mice specific Toxoplasrna antibody in serum was detected from the 4th day in type II infection group, and remained increase after that until the 64th day, while type III group got the peak earlier at the 32nd day. Interestingly, the three strains showed similar distribution features in mice organs： in early stage （the 1st day）, parasites were detected in lung, kidney and muscle, then appeared in heart, lung, muscle and brain in midterm （the 8th day）, at last （the 32nd day） brain was the only detected organ. During infection, parasites were not be detected in spleen and liver. Our work successfully built up a Toxoplasrna infection mice model of three strains and demonstrated their pathogenicity in detail. In addition, there was a certain similar regularity on mice organ distribution at different time among different Toxoplasrna genotypes infection, which means organ tropism along time. Our results give reference for Toxoplasma pathogenicity and establishment of its animal infection model.